Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy (ExCell)

A Multi-Center, Multi-National, Historical Cohort Controlled Study to Evaluate Efficacy and Safety of Transplantation of StemEx®, Umbilical Cord Blood Stem and Progenitor Cells Expanded Ex Vivo, in Subjects With Hematologic Malignancies Following Myeloablative Therapy

The purpose of this study is to determine the efficacy and safety of transplanting StemEx® in patients with certain hematological malignancies. For these patients, it is suggested that StemEx® can improve upon the outcome of transplanting a single, unmanipulated cord blood unit by significantly increasing the number of stem/progenitor cells available to the patient.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Non-Hodgkin's Lymphoma; Chronic Myeloid Leukemia; Hematologic Malignancies; Hodgkin's Disease; Lymphoid Leukemia
• Intervention / Treatment: Drug: StemEx®

Detailed Description

Allogeneic hematopoietic stem cell transplantation is a life-saving procedure for patients with hematologic malignancies; yet wide application of this procedure is limited by the availability of suitably Human Leukocyte Antigen (HLA) - matched donors. Only 30% of patients who could benefit from this procedure have an HLA-matched sibling. The lengthy search for a matched donor may critically delay transplantation. In addition, far fewer patients of racial minorities find suitable HLA-matched donors. Umbilical cord blood (UCB) has been increasingly used as an alternative source of stem cells; however, its use in adults and adolescent patients is limited due to insufficient cell dose required for satisfactory hematopoietic reconstitution.

Gamida Cell - Teva Joint Venture Ltd. is engaged in the development of StemEx®, an expanded hematopoietic UCB stem cell graft, as a potential medicinal product for the treatment of cancer and hematological malignancies. The expansion technology enables preferential expansion of hematopoietic stem and early progenitor cells and is based on the findings that copper chelators can regulate the balance between self-renewal and differentiation of stem cells.

The multi-national, multi-center Phase II/III clinical study designated to evaluate the safety and efficacy of StemEx® will enroll approximately 100 subjects with high-risk hematologic malignancies who are candidates for allogeneic stem cell transplantation (SCT). This study will evaluate the effect of StemEx® on overall survival as measured by overall 100-day mortality.

The study consists of 4 phases:

1. Screening phase includes subjects' clinical assessment and screening tests
2. Conditioning phase includes the myeloablative treatment prior transplantation procedure
3. Transplantation and post-transplant follow-up phase to day 180
4. Observational phase: survival status follow-up to day 730 (18 months)

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1097
    • Szent Laszlo & Szent Istvan Hospital
• Israel
  • Jerusalem, Israel, P.O.B 12000
    • Hebrew University Hospital Ein-Karem, Department of Bone Marrow Transplantation And Cancer Immunotherapy
  • PO Box 9602, Haifa, Israel, 31096
    • Rambam Medical Center
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
• Italy
  • Roma, Italy, 00165
    • Ospedale Pedriatrico Bambino Gesù
  • Viale Morgagni, Florence, Italy, 85 - 50134
    • Ospedale di Careggi BMT Unit Department of Haematology
  • via Oxford 81, Roma, Italy, 00133
    • Universita Di Roma Tor Vergata
• Spain
  • Av Campanar 21, Valencia, Spain, 46009
    • Hospital Universitario La Fe
  • C/ Sant Antoni Maria Claret, Barselona, Spain, 167 - 08025
    • Hospital de la Santa Creu i Sant Pau
  • Carretera de Canyet s/n, Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Doctor Esquerdo 46 , Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Passeig de la Vall d´Hebrón 119-129, Barcelona, Spain, 08035
    • Hospital Universitario Vall d´Hebrón (Pediatrics)
  • Passeig de la Vall d´Hebrón 119-129, Barcelona, Spain, 08035
    • Hospital Universitario Vall d´Hebron
  • Comunidad Valenciana
    • Avda. Blasco Ibañez, 17, Valencia, Comunidad Valenciana, Spain, 46010
      • Hospital Clinico Universitario de Valencia
• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • UCLA's Jonsson Comprehensive Cancer Center
    • Orange, California, United States, 92868-3874
      • Children's Hospital of Orange County
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital, B115, University of Colorado Health Sciences Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center, Loyola University Stritch School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • The Cancer Center at Hackensack University Medical Center
  • New York
    • New York, New York, United States, NY 10065
      • Cornell University, Joan & Sanford I. Weill Medical College
    • New York, New York, United States
      • Steven And Alexandra Cohen Children's Medical Center Of New York
    • One Gustave L Levy Place, BOX 1410, New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • The Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute/UPMC Cancer Centers
  • Texas
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute
  • Virginia
    • West Complex 1300 Jefferson Park Av, Charlottesville, Virginia, United States, 22903
      • University of Virginia, Hematopoietic Stem Cell Transplant Program
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Division of Neoplastic Diseases and Related Disorders
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Pediatric Blood and Marrow Transplant Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical diagnosis of AML or ALL: CR2 or subsequent complete remission (CR) or CR1 with high-risk features or relapse with < 10% blasts in BM and no circulating blasts.
2. Clinical diagnosis of CML: in CP1 (Chronic Phase 1) and resistant or intolerant to Gleevec or in CP2 or subsequent CP or in accelerated phase.
3. Clinical diagnosis of HD: induction failure or relapse and sensitive to last chemotherapy course.
4. Clinical diagnosis of NHL induction failure or relapse and sensitive to last chemotherapy course.
5. Clinical diagnosis of MDS with intermediate 2- or high-risk IPSS score.

Exclusion Criteria:

1. Less than twenty-one days have elapsed since the subject's last radiation or chemotherapy prior to conditioning (except Hydroxyurea).
2. HIV positive.
3. Pregnancy or lactation.
4. Uncontrolled bacterial, fungal or viral infection.
5. Subjects with signs and symptoms of active central nervous system (CNS) disease.
6. Availability of appropriate related and willing stem cell donor, who is HLA-matched at 5 or 6/6 antigens.
7. Prior allogeneic cell transplant.
8. Allergy to bovine or to any product, which may interfere with the treatment.
9. Enrolled in another clinical trial or received an investigational treatment during the last 30 days, unless approved by Sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: StemEx	Drug: StemEx®; The stem/progenitor cell based product composed of ex vivo expanded allogeneic umbilical cord blood cells, which is infused to subject at a rate of 1-3 ml/min in combination with non-manipulated cells derived from the same cord blood unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall 100-day mortality	100 days

Secondary Outcome Measures

Outcome Measure	Time Frame
180 day mortality, acute Graft versus Host Disease (GvHD) grades III-IV, engraftment failure	180 days
Safety and tolerability measures: The incidence and frequency of adverse experiences, acute toxicity, laboratory data and vital signs follow-up.	180 days
Proportion of overall mortality at 1 year	One year post transplant
Proportion of overall mortality at 2 years	Two years post transplant

Collaborators and Investigators

• Sponsor: Gamida Cell -Teva Joint Venture Ltd.
• Investigators: Principal Investigator: Ka Wah Chan, MD, Texas Transplant Institute; Principal Investigator: Scott D Rowley, MD, The Cancer Center at Hackensack University Medical Center; Principal Investigator: Mary Territo, MD, UCLA Oncology Center; Principal Investigator: Patrick Stiff, MD, Loyola University Cardinal Bernardin Cancer Center; Principal Investigator: Agha Mounzer, MD, University of Pittsburgh Cancer Institute/UPMC Cancer Centers; Principal Investigator: Entezam Sahovic, MD, The Western Pennsylvania Hospital; Principal Investigator: Celia Grosskreutz, MD, Icahn School of Medicine at Mount Sinai; Principal Investigator: Roger Giller, MD, The Children's Hospital, B115, University of Colorado Health Sciences Center; Principal Investigator: Steven Neudorf, MD, Children's Hospital of Orange County; Principal Investigator: Ronit Yerushalmi, MD, Chaim Sheba Medical Center; Principal Investigator: Tsila Zuckerman, MD, Rambam Health Care Campus; Principal Investigator: Christelle Ferra, MD, Germans Trias i Pujol Hospital; Principal Investigator: Cristina Arbona, MD, Hospital Clinico Universitario de Valencia; Principal Investigator: Guillermo Sanz, MD, Hospital Universitario La Fe; Principal Investigator: William Arcese, MD, Universita Di Roma Tor Vergata; Principal Investigator: Alberto Bosi, MD, Ospedale di Careggi BMT Unit Department of Haematology; Principal Investigator: Sonali Chaudhury, MD, Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital; Principal Investigator: Igor B. Resnick, MD, PhD, Department of Bone Marrow Transplantation And Cancer Immunotherapy Hebrew University Hospital Ein-Karem, Jerusalem; Principal Investigator: Prof. Franco Locatelli, MD, Ospedale Pedriatrico Bambino Gesù; Principal Investigator: Dr. Mi Kwon, MD, Hospital General Universitario Gregorio Marañón; Principal Investigator: Dr. Pere Barba, MD, Hospital Universitario Vall d´Hebron; Principal Investigator: Dr. Cristina Diaz de Heredia, MD, Hospital Universitario Vall d´Hebron; Principal Investigator: Prof. Mary J Laughlin, MD, Hematopoietic Stem Cell Transplant Program, University of Virginia

Publications and helpful links

General Publications

• Peled T, Landau E, Prus E, Treves AJ, Nagler A, Fibach E. Cellular copper content modulates differentiation and self-renewal in cultures of cord blood-derived CD34+ cells. Br J Haematol. 2002 Mar;116(3):655-61. doi: 10.1046/j.0007-1048.2001.03316.x. Erratum In: Br J Haematol 2002 May;117(2):485.
• Peled T, Landau E, Mandel J, Glukhman E, Goudsmid NR, Nagler A, Fibach E. Linear polyamine copper chelator tetraethylenepentamine augments long-term ex vivo expansion of cord blood-derived CD34+ cells and increases their engraftment potential in NOD/SCID mice. Exp Hematol. 2004 Jun;32(6):547-55. doi: 10.1016/j.exphem.2004.03.002.
• Prus E, Peled T, Fibach E. The effect of tetraethylenepentamine, a synthetic copper chelating polyamine, on expression of CD34 and CD38 antigens on normal and leukemic hematopoietic cells. Leuk Lymphoma. 2004 Mar;45(3):583-9. doi: 10.1080/10428190310001598035.
• Peled T, Mandel J, Goudsmid RN, Landor C, Hasson N, Harati D, Austin M, Hasson A, Fibach E, Shpall EJ, Nagler A. Pre-clinical development of cord blood-derived progenitor cell graft expanded ex vivo with cytokines and the polyamine copper chelator tetraethylenepentamine. Cytotherapy. 2004;6(4):344-55. doi: 10.1080/14653240410004916.
• Peled T, Glukhman E, Hasson N, Adi S, Assor H, Yudin D, Landor C, Mandel J, Landau E, Prus E, Nagler A, Fibach E. Chelatable cellular copper modulates differentiation and self-renewal of cord blood-derived hematopoietic progenitor cells. Exp Hematol. 2005 Oct;33(10):1092-100. doi: 10.1016/j.exphem.2005.06.015.
• Shpall EJ, M.d.L., K. Chan, R. Champlin, A. Gee, P. Thall, K. Komanduri, D. Couriel, C. Hosing, B. Andersson, R. Jones, S. Giralt, S. Karandish, T. Sadeghi, B. Muriera, S. O'Connor, L. Wooten, X. Wang, S. Robinson, P. Fu, J. Wilson, T. Peled, F. Grynspan, A. Nagler, J. McMannis; A Phase I/II Study of Ex Vivo Expanded Cord Blood for Leukemia and Lymphoma. ISCT 2005 - conference publication, 2005.
• de Lima M, McMannis J, Gee A, Komanduri K, Couriel D, Andersson BS, Hosing C, Khouri I, Jones R, Champlin R, Karandish S, Sadeghi T, Peled T, Grynspan F, Daniely Y, Nagler A, Shpall EJ. Transplantation of ex vivo expanded cord blood cells using the copper chelator tetraethylenepentamine: a phase I/II clinical trial. Bone Marrow Transplant. 2008 May;41(9):771-8. doi: 10.1038/sj.bmt.1705979. Epub 2008 Jan 21.
• Stiff PJ, Montesinos P, Peled T, Landau E, Goudsmid NR, Mandel J, Hasson N, Olesinski E, Glukhman E, Snyder DA, Cohen EG, Kidron OS, Bracha D, Harati D, Ben-Abu K, Freind E, Freedman LS, Cohen YC, Olmer L, Barishev R, Rocha V, Gluckman E, Horowitz MM, Eapen M, Nagler A, Sanz G. Cohort-Controlled Comparison of Umbilical Cord Blood Transplantation Using Carlecortemcel-L, a Single Progenitor-Enriched Cord Blood, to Double Cord Blood Unit Transplantation. Biol Blood Marrow Transplant. 2018 Jul;24(7):1463-1470. doi: 10.1016/j.bbmt.2018.02.012. Epub 2018 Mar 1.

Helpful Links

• Sponsor's website
• Bone and Marrow Transplant Information Network
• NCI Leukemia Homepage
• Leukemia information on MediciNet.com
• American Society for Blood and Marrow Transplantation
• American Society of Hematology
• Lymphoma Research Foundation
• American Cancer Society website
• Cord Blood Forum
• Center for International Blood and Marrow Transplant Research
• National Marrow Donor Program
• Children's Hospital of Orange County
• University of Colorado Cancer Center
• Northwestern University School of Medicine, Stem Cell Transplant Program, Children's Memorial Hospital website
• Mount Sinai Medical Center
• Duke University Medical Center
• Case Western Reserve University
• University of Pittsburgh Cancer Institute
• MD Anderson Cancer Center
• Texas Transplant Institute
• Hôpital Saint Louis
• Chaim Sheba Medical Center
• Rambam Medical Center
• Universita di Roma Tor Vergata
• Ospedale di Careggi BMT Unit Department of Haematology
• Hospital Germans Trias i Pujol
• Hospital Clinic of Barcelona
• Hospital de la Santa Creu i Sant Pau
• ULCA

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 4, 2007

Study Record Updates

• Last Update Posted (Estimate): July 10, 2015
• Last Update Submitted That Met QC Criteria: July 9, 2015
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: Umbilical Cord Blood Stem Cell Transplantation; Hematological Malignancies; Acute Lymphoid Leukemia; Tetraethylenepentamine; Subjects with high-risk hematologic malignancies who are candidates for allogeneic stem cell transplantation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Lymphoma; Neoplasms; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Leukemia, Myeloid; Hodgkin Disease; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: GC P#02.01.001